A Study to Learn More About How Well Elinzanetant Works and How Safe it is for the Treatment of Vasomotor Symptoms (Hot Flashes) That Are Caused by Hormonal Changes Over 26 Weeks in Women Who Have Been Through the Menopause (OASIS-2)

Bayer

Status and phase: Completed; Phase 3

Conditions: Hot Flashes; Vasomotor Symptoms Associated With Menopause

Treatments: Drug: Placebo; Drug: Elinzanetant (BAY3427080)

Study type: Interventional

Funder types: Industry

Identifiers

NCT05099159

2020-004855-34 (EudraCT Number)

21652

Details and patient eligibility

About

Researchers are looking for a better way to treat women who have hot flashes after women have been through the menopause. Hot flashes are caused by the hormonal changes that happen when a woman's body has been through the menopause. Menopause is when women stop having a menstrual cycle, also called a period. During the menopause, the ovaries increasingly produce less sex hormones as a result of the natural ageing process and related hormonal adjustments. The decline in hormone production can lead to various symptoms which, in some cases, can have a very adverse effect on a menopausal woman's quality of life.

The study treatment, elinzanetant, was developed to treat symptoms caused by hormonal changes. It works by blocking a protein called neurokinin from sending signals to other parts of the body, which is thought to play a role in starting hot flashes. There are treatments for hot flashes in women who have been through the menopause, but may cause medical problems for some people.

In this study, the researchers will learn how well elinzanetant works compared to a placebo in women who have been through the menopause and have hot flashes. A placebo looks like a treatment but does not have any medicine in it. To compare these study treatments, the doctors will ask the participants to record information about the participants' hot flashes in an electronic diary. The researchers will study the number of hot flashes the participants have and how severe the hot flashes are. The researchers will look at the results from before treatment, after 4 weeks, and after 12 weeks of treatment.

The participants in this study will take two capsules of either elinzanetant or the placebo once a day. The participants who take elinzanetant will take it for 26 weeks. The participants who take the placebo will take it for 12 weeks and then take elinzanetant for the next 14 weeks.

During the study, the participants will visit the site approximately 9 times and perform 1 visit by phone. Each participant will be in the study for approximately 36 weeks. The treatment duration will be 26 weeks.

During the study, the participants will:

• record information about the participants' hot flashes in an electronic diary
• answer questions about the participants' symptoms

The doctors will:

• check the participants' health
• take blood samples
• ask the participants questions about what medicines the participants are taking and if the participants are having adverse events An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if doctors do not think the adverse events might be related to the study treatments.

Enrollment: 400 patients

Sex: Female

Ages: 40 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Postmenopausal, defined as:

  1. at least 12 months of spontaneous amenorrhea prior to signing of informed consent, or
  2. at least 6 months of spontaneous amenorrhea prior to signing of informed consent with serum follicle-stimulating hormone (FSH) levels > 40 mIU/mL and a serum estradiol concentration of < 30 pg/mL, or
  3. at least 6 months after hysterectomy at signing of informed consent with serum FSH levels > 40 mIU/mL and a serum estradiol concentration of < 30 pg/mL, or
  4. surgical bilateral oophorectomy with or without hysterectomy at least 6 weeks prior to signing of informed consent.

• Moderate to severe hot flash (HF) associated with the menopause and seeking treatment for this condition.

• Participant has completed Hot Flash Daily Diary (HFDD) for at least 11 days during the two weeks preceding baseline visit, and participant has recorded at least 50 moderate or severe HF (including night-time HF) over the last 7 days that the HFDD was completed (assessed at the Baseline Visit).

Exclusion criteria

• Any clinically significant prior or ongoing history of arrhythmias, heart block and QT prolongation either determined through clinical history or on ECG evaluation.

• Any active ongoing condition that could cause difficulty in interpreting vasomotor symptoms (VMS) such as: infection that could cause pyrexia, pheochromocytoma, carcinoid syndrome.

• Current or history (except complete remission for 5 years or more) of any malignancy (except basal and squamous cell skin tumors). Women receiving adjuvant endocrine therapy (e.g. tamoxifen, aromatase inhibitors, GnRH analogues) cannot be enrolled in this study.

• Uncontrolled or treatment-resistant hypertension. Women with mild hypertension can be included in the study if they are medically cleared prior to study participation.

• Untreated hyperthyroidism or hypothyroidism.

  • Treated hyperthyroidism with no abnormal increase of thyroid function laboratory parameters and no relevant clinical signs for > 6 months before signing of informed consent is acceptable.
  • Treated hypothyroidism with normal thyroid function test results during screening and a stable (for ≥ 3 months before signing of informed consent) dose of replacement therapy is acceptable.

• Any unexplained post-menopausal uterine bleeding.

• Clinically relevant abnormal findings on mammogram.

• Abnormal liver parameters.

• Disordered proliferative endometrium, endometrial hyperplasia, polyp, or endometrial cancer diagnosed based on endometrial biopsy during screening.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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400 participants in 2 patient groups, including a placebo group

Elinzanetant (BAY3427080)

Experimental group

Description:

Participants will receive 120 mg elinzanetant orally once daily for 26 weeks.

Treatment:

Drug: Elinzanetant (BAY3427080)

Placebo + elinzanetant

Placebo Comparator group

Description:

Participants will receive matching placebo orally once daily for 12 weeks, followed by elinzanetant 120 mg for 14 weeks.

Treatment:

Drug: Elinzanetant (BAY3427080)

Drug: Placebo